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Mammalian cells do not have a stringent response

J W Pollard, T Lam, C P Stanners

    Journal of Cellular Physiology
    |November 1, 1980
    PubMed
    Summary
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    Mammalian cells do not exhibit a stringent response analogous to bacteria, as amino acid starvation did not inhibit ribosomal RNA synthesis or produce unusual nucleotides. This suggests a lack of a similar macromolecular control system in mammals.

    Area of Science:

    • Cellular Biology
    • Molecular Biology
    • Biochemistry

    Background:

    • Bacteria possess a stringent response, a key survival mechanism involving inhibition of ribosomal RNA synthesis.
    • This response is triggered by uncharged transfer RNA (tRNA) and mediated by unusual nucleotides.
    • The existence of an analogous stringent response in mammalian cells remains uncharacterized.

    Purpose of the Study:

    • To investigate whether mammalian cells exhibit a stringent response similar to bacteria.
    • To determine if amino acid starvation in mammalian cells leads to inhibition of ribosomal RNA synthesis.
    • To examine the role of uncharged tRNA and unusual nucleotides in mammalian cellular responses.

    Main Methods:

    • Mammalian cells (normal and transformed CHO cells, Chinese hamster embryo fibroblasts) were subjected to rapid amino acid starvation (leucine or histidine).

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  • Ribosomal RNA (rRNA) synthesis and maturation were measured using (3H-methyl) methionine.
  • Intracellular nucleotide pools were analyzed for changes in guanosine tetraphosphate/pentaphosphate and normal nucleotides.
  • Protein synthesis inhibition was controlled using cycloheximide.

    • Main Results:

    • Rapid generation of uncharged tRNA did not affect pre-ribosomal RNA synthesis in any tested cell type.
    • A nonspecific inhibition of 18S rRNA maturation and late pre-rRNA synthesis was observed, but mimicked by cycloheximide.
    • Severe amino acid starvation did not induce unusual nucleotides (e.g., guanosine tetraphosphate) or alter normal nucleotide levels.
    • Protein synthesis inhibition to 30% showed no specific effect on pre-rRNA synthesis and maturation.

    Conclusions:

    • Mammalian cells do not possess a macromolecular control system analogous to the bacterial stringent response.
    • While mammalian cells may react biochemically to uncharged tRNA, they lack the coordinated regulatory network seen in bacteria.
    • The study provides evidence against a direct mammalian homolog of the bacterial stringent response mechanism.